Alzheimer's disease is a brain disease that slowly destroys memory and thinking skills, up to loss of the ability to carry out the simplest tasks. It is the most common cause of dementia among older people. Mild. Alzheimer's disease manifests itself in memory loss and small changes in other cognitive abilities, e.g., getting lost, trouble handling money and managing daily tasks, having some mood and personality changes, etc. In the stage of Moderate Alzheimer's disease, the control of language, reasoning, sensory processing, and conscious thought are impacted. Memory loss and confusion grow worse, e.g., patients have problems recognizing family and friends and become unable to learn new things, etc. hallucinations, delusions, and paranoia may occur. Severe Alzheimer's disease is the final stage. Patients cannot communicate anymore and are completely dependent on others.
N-[(3S)-1-[4-[(3-fluorophenyl)methoxy]phenyl]-5-oxo-pyrrolidin-3-yl]acetamide has previously been described in WO2001/026825. WO 2006/097197 and WO 2006/097270 relate to methods for preparing enantiomerically pure 4-pyrrolidinophenylbenzyl ether derivatives.
The processes of the prior art have several drawbacks (e.g., long reaction sequence, low overall yield also due to loss of half of the product in the classical resolution step, the need for a chromatographic purification to remove by-products formed in the Mitsunobu reaction) and are therefore less suitable for the preparation of N-[(3 S)-1-[4-[(3-fluorophenyl) methoxy]phenyl]-5-oxo-pyrrolidin-3-yl]acetamide on large scale.
Object of the present invention is to provide an improved and high yielding process which avoids these drawbacks and which is suitable for the large scale manufacture of N-[(3 S)-1-[4-[(3-fluorophenyl)methoxy]phenyl]-5-oxo-pyrrolidin-3-yl]acetamide 1.